NRU :: Browsing by Author "Redd, Andrew D."

Browsing by Author "Redd, Andrew D."

Now showing 1 - 11 of 11

Decreased Monocyte Activation with daily Acyclovir use in HIV-1/HSV-2 Coinfected Women
(Sexually transmitted infections, 2015) Redd, Andrew D.; Nalugoda, Fred; Ssebbowa, Paschal; Kalibbala, Sarah
Several clinical trials have demonstrated that daily treatment of HIV-infected individuals with the antiherpes drug acyclovir slightly decreases HIV-1 viral load and slows disease progression. This study examines if this slowing in clinical progression is a direct cause of the decrease in viral load or an indirect effect of lower immune activation due to lower levels of herpetic reactivation. Women who participated in a randomised clinical trial of daily acyclovir use (n=301) were monitored every 6 months for changes in immune activation. Soluble CD14 (sCD14), a marker for monocyte activation, and C-reactive protein (CRP), a marker for general immune activation, were measured by ELISA.Initial levels of sCD14 and CRP were not predictive of HIV disease progression when controlling for initial CD4+ cell count and HIV viral load. sCD14 levels, but not CRP, decreased in the acyclovir treatment arm at a significantly faster rate than the placebo group, which was independent of changes in HIV viral load and CD4+ cell count in a multivariant mixed-effects model (p=0.039). However, the magnitude of this decrease was relatively small with a total estimated decrease of sCD14 of 15% of initial levels.These data suggest that decreased monocyte activation may play a minor role in the ability of daily acyclovir use to slow HIV disease progression.
Hepatitis E Virus Seroprevalence and Correlates of Anti-HEV IgG Antibodies in the Rakai District, Uganda
(The Journal of Infectious Diseases, 2018) Boon, Denali; Redd, Andrew D.; Laeyendecker, Oliver; Engle, Ronald E.; Nguyen, Hanh; Ocama, Ponsiano; Boaz, Iga; Ndyanabo, Anthony; Kiggundu, Valerian; Reynolds, Steven J.; Gray, Ronald H.; Wawer, Maria J.; Purcell, Robert H.; Kirk, Gregory D.; Quinn, Thomas C.; Stabinski, Lara
A cross-sectional study was conducted of 500 human immunodeficiency virus (HIV)-infected adults frequency matched on age, sex, and community to 500 HIV-uninfected individuals in the Rakai District, Uganda to evaluate seroprevalence of anti-hepatitis E virus (HEV) IgG antibodies. HEV seroprevalence was 47%, and 1 HIV-infected individual was actively infected with a genotype 3 virus. Using modified Poisson regression, male sex (prevalence ratios [PR] = 1.247; 95% confidence interval [CI], 1.071–1.450) and chronic hepatitis B virus infection (PR = 1.377; 95% CI, 1.090–1.738) were associated with HEV seroprevalence. HIV infection status (PR = 0.973; 95% CI, 0.852–1.111) was not associated with HEV seroprevalence. These data suggest there is a large burden of prior exposure to HEV in rural Uganda.
High proportion of Ugandans with pre-pandemic SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell responses
(medRxiv, 2023) Namuniina, Annemarie; Muyanja, Enoch S.; Biribawa, Victoria M.; Ssemaganda, Aloysious; Nanteza, Ann; Bagaya, Bernard Ssentalo; Galwango, Ronald M.; Redd, Andrew D.
The estimated mortality rate of the SARS-CoV-2 pandemic varied greatly around the world with multiple countries in East, Central, and West Africa having significantly lower rates of COVID-19 related fatalities than many resource-rich nations with significantly earlier wide-spread access to life-saving vaccines. One possible reason for this lower mortality could be the presence of pre-existing cross-reactive immunological responses in these areas of the world. To explore this hypothesis, stored peripheral blood mononuclear cells (PBMC) from Ugandans collected from 2015-2017 prior to the COVID-19 pandemic (n=29) and from hospitalized Ugandan COVID-19 patients (n=3) were examined using flow-cytometry for the presence of pre-existing SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell populations using four T-cell epitope mega pools. Of pre-pandemic participants, 89.7% (26/29) had either CD4+ or CD8+, or both, SARS-CoV-2 specific T-cell responses. Specifically, CD4+ T-cell reactivity (72.4%) and CD8+ T-cell reactivity (65.5%) were relatively similar, and 13 participants (44.8%) had both types of cross-reactive types of T-cells present. There were no significant differences in response by sex in the population. The rates of cross-reactive T-cell populations in these Ugandans is higher than previous estimates from resource-rich countries like the United States (20-50% reactivity). It is unclear what role, if any, this cross-reactivity played in decreasing COVID-19 related mortality in Uganda and other African countries, but does suggest that a better understanding of global pre-existing immunological cross-reactivity could be an informative data of epidemiological intelligence moving forward.
HIV-1 superinfection can occur in the presence of broadly neutralizing antibodies
(Vaccine, 2018) Serwanga, Jennifer; Ssemwanga, Deogratius; Muganga, Michael; Nakiboneka, Ritah; Nakubulwa, Susan; Kiwuwa-Muyingo, Sylvia; Morris, Lynn; Redd, Andrew D.; Quinn, Thomas C.; Kaleebu, Pontiano
Superinfection of individuals already infected with HIV-1 suggests that pre-existing immune responses may not adequately protect against re-infection. We assessed high-risk female sex workers initially infected with HIV-1 clades A, D or A/D recombinants, to determine if HIV-1 broadly neutralizing antibodies were lacking prior to superinfection. Methods: Six superinfected female sex workers previously stratified by HIV-1 high-risk behavior, infecting virus clade and volunteer CD4 counts were evaluated at baseline (n = 5) and at 350 days post-superinfection (n = 6); one superinfected volunteer lacked pre-superinfection plasma. Retrospective plasmas were assessed for neutralization of a multi-clade panel of 12 HIV-1 viruses before superinfection, and then at quarterly intervals thereafter. Similarly stratified singly infected female sex workers were correspondingly assessed at baseline (n = 19) and 350 days after superinfection (n = 24). Neutralization of at least 50% of the 12 viruses (broad neutralization), and geometric means of the neutralization titers (IC50) were compared before and after superinfection; and were correlated with the volunteer HIV-1 superinfection status, CD4 counts, and pseudovirus clade. Results: Preexisting broad neutralization occurred in 80% (4/5) of the superinfected subjects with no further broadening by 350 days after superinfection. In one of the five subjects, HIV-1 superinfection occurred when broad neutralization was lacking; with subsequent broadening of neutralizing antibodies occuring within 9 months and plateauing by 30 months after detection of superinfection. Clade B and C pseudoviruses were more sensitive to neutralization (13; [87%]); and (12; [80%]) than the locally circulating clades A (10; [67%]) and D (6; [40%]), respectively (p = 0.025). Low antibody titers correlated with clade D viruses and with >500 CD4 T cell counts, but not with the superinfection status. Conclusion: These data demonstrate that HIV-1 superinfection can occur both in the presence, and in the absence of broadly neutralizing antibodies.
Immunological Signaling During Herpes Simplex Virus-2 and Cytomegalovirus Vaginal Shedding After Initiation of Antiretroviral Treatment
(Oxford University Press, 2016) Nason, Martha C.; Patel, Eshan U.; Kirkpatrick, Allison R.; Prodger, Jessica L.; Shahabi, Kamnoosh; Tobian, Aaron A. R.; Gianella, Sara; Kalibbala, Sarah; Ssebbowa, Paschal; Kaul, Rupert; Gray, Ronald H.; Quinn, Thomas C.; Serwadda, David; Reynolds, Steven J.; Redd, Andrew D.
Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)-α, and interferon- γ. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-α (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation.
Liver Stiffness Is Associated With Monocyte Activation in HIV-Infected Ugandans Without Viral Hepatitis
(AIDS research and human retroviruses, 2013) Redd, Andrew D.; Wendel, Sarah K.; Grabowski, Mary K.; Ocama, Ponsiano; Kiggundu, Valerian; Bbosa, Francis; Boaz, Iga; Balagopal, Ashwin; Reynolds, Steven J.; Gray, Ronald H.; Serwadda, David; Kirk, Gregory D.; Quinn, Thomas C.; Stabinski, Lara
A high prevalence of liver stiffness, as determined by elevated transient elastography liver stiffness measurement, was previously found in a cohort of HIV-infected Ugandans in the absence of chronic viral hepatitis. Given the role of immune activation and microbial translocation in models of liver disease, a shared immune mechanism was hypothesized in the same cohort without other overt causes of liver disease. This study examined whether HIV-related liver stiffness was associated with markers of immune activation or microbial translocation (MT). A retrospective case-control study of subjects with evidence of liver stiffness as defined by a transient elastography stiffness measurement ‡ 9.3 kPa (cases = 133) and normal controls (n = 133) from Rakai, Uganda was performed. Cases were matched to controls by age, gender, HIV, hepatitis B virus (HBV), and highly active antiretroviral therapy (HAART) status. Lipopolysaccharide (LPS), endotoxin IgM antibody, soluble CD14 (sCD14), C-reactive protein (CRP), and D-dimer levels were measured. Conditional logistic regression was used to estimate adjusted matched odds ratios (adjMOR) and 95% confidence intervals. Higher sCD14 levels were associated with a 19% increased odds of liver stiffness (adjMOR = 1.19, p = 0.002). In HIV-infected individuals, higher sCD14 levels were associated with a 54% increased odds of having liver stiffness (adjMOR = 1.54, p < 0.001); however, the opposite was observed in HIV-negative individuals (adjMOR = 0.57, p = 0.001). No other biomarker was significantly associated with liver stiffness, and only one subject was found to have detectable LPS. Liver stiffness in HIV-infected Ugandans is associated with increased sCD14 indicative of monocyte activation in the absence of viral hepatitis or microbial translocation, and suggests that HIV may be directly involved in liver disease.
Microbial translocation, the innate cytokine response, and HIV-1 disease progression in Africa
(National Academy of Sciences, 2009) Redd, Andrew D.; Dabitao, Djeneba; Bream, Jay H.; Charvat, Blake; Laeyendecker, Oliver; Kiwanuka, Noah; Lutalo, Tom; Kigozi, Godfrey; Tobian, Aaron A. R.; Gamiel, Jordyn; Neal, Jessica D.; Oliver, Amy E.; Margolick, Joseph B.; Reynolds, Steven J.; Sewankambo, Nelson K.; Wawer, Maria J.; Serwadda, David; Gray, Ronald H.; Quinn, Thomas C.
Reports from the United States have demonstrated that elevated markers of microbial translocation from the gut may be found in chronic and advanced HIV-1 infection and are associated with an increase in immune activation. However, this phenomenon’s role in HIV-1 disease in Africa is unknown. This study examined the longitudinal relationship between microbial translocation and circulating inflammatory cytokine responses in a cohort of people with varying rates of HIV-1 disease progression in Rakai, Uganda. Multiple markers for microbial translocation (lipopolysaccharide, endotoxin antibody, and sCD14) did not change significantly during HIV-1 disease progression. Moreover, circulating immunoreactive cytokine levels either decreased or remained virtually unchanged throughout disease progression. These data suggest that microbial translocation and its subsequent inflammatory immune response do not have a causal relationship with HIV-1 disease progression in Africa.
Previously Transmitted HIV-1 Strains Are Preferentially Selected During Subsequent Sexual Transmissions
(The Journal of infectious diseases, 2012) Redd, Andrew D.; Collinson-Streng, Aleisha N.; Chatziandreou, Nikolaos; Mullis, Caroline E.; Laeyendecker, Oliver; Martens, Craig; Ricklefs, Stacy; Kiwanuka, Noah; Hninn Nyein, Phyu; Grabowski, Mary K.; Kong, Xiangrong; Manucci, Jordyn; Sewankambo, Nelson; Wawer, Maria J.; Gray, Ronald H.; Porcella, Stephen F.; Fauci, Anthony S.; Sagar, Manish; Serwadda, David; Quinn, Thomas C.
A genetic bottleneck is known to exist for human immunodeficiency virus (HIV) at the point of sexual transmission. However, the nature of this bottleneck and its effect on viral diversity over time is unclear. Methods. Interhost and intrahost HIV diversity was analyzed in a stable population in Rakai, Uganda, from 1994 to 2002. HIV-1 envelope sequences from both individuals in initially HIV-discordant relationships in which transmission occurred later were examined using Sanger sequencing of bulk polymerase chain reaction (PCR) products (for 22 couples), clonal analysis (for 3), and next-generation deep sequencing (for 9). Results. Intrahost viral diversity was significantly higher than changes in interhost diversity (P < .01). The majority of HIV-1–discordant couples examined via bulk PCR (16 of 22 couples), clonal analysis (3 of 3), and next-generation deep sequencing (6 of 9) demonstrated that the viral populations present in the newly infected recipient were more closely related to the donor partner’s HIV-1 variants found earlier during infection as compared to those circulating near the estimated time of transmission (P = .03). Conclusions. These findings suggest that sexual transmission constrains viral diversity at the population level, partially because of the preferential transmission of ancestral as opposed to contemporary strains circulating in the transmitting partner. Future successful vaccine strategies may need to target these transmitted ancestral strains.
The rates of HIV-1 superinfection and primary HIV-1 infection are similar in female sex workers in Uganda
(Theoretical Medicine and Bioethics, 2008) Redd, Andrew D.; Ssemwanga, Deogratius; Vandepitte, Judith; Wendel, Sarah K.; Ndembi, Nicaise; Bukenya, Justine; Nakubulwa, Susan; Grosskurth, Heiner; Parry, Chris M.; Martens, Craig; Bruno, Daniel; Porcella, Stephen F.; Quinn, Thomas C.; Kaleebu, Pontiano
To determine and compare the rates of HIV superinfection and primary HIV infection in high-risk female sex workers in Kampala, Uganda. Design—A retrospective analysis of individuals who participated in a clinical cohort study among high-risk female sex workers in Kampala, Uganda. Methods—Plasma samples from HIV-infected female sex workers (FSW) in Kampala, Uganda were examined with next-generation sequencing of the p24 and gp41HIV genomic regions for the occurrence of superinfection. Primary HIV incidence was determined from initially HIV-uninfected FSW from the same cohort, and incidence rate ratios were compared. Results—The rate of superinfection in these women (7/85; 3.4/100py) was not significantly different from the rate of primary infection in the same population (3.7/100py; IRR=0.91, p=0.42). Seven women also entered the study dual infected (16.5% either dual or superinfected). The women with any presence of dual infection were more likely to report sex work as their only source of income (p=0.05), and trended to be older and more likely to be widowed (p=0.07). Conclusions—In this cohort of female sex workers, HIV superinfection occurred at a high rate and was similar to that of primary HIV infection. These results differ from a similar study of high-risk female bar-workers in Kenya that found the rate of superinfection to be significantly lower than the rate of primary HIV infection.
Short Communication Colony-Forming Hematopoietic Progenitor Cells Are Not Preferentially Infected by HIV Type 1 Subtypes A and D in Vivo
(AIDS research and human retroviruses, 2012) Mullis, Caroline E.; Oliver, Amy E.; Eller, Leigh Anne; Guwatudde, David; Mueller, Amy C.; Eller, Michael A.; Kibuuka, Hannah; Robb, Merlin; Quinn, Thomas C.; Redd, Andrew D.
HIV subtype C has previously been shown to infect hematopoietic progenitor cells (HPCs) at a significantly higher rate than subtype B. To better understand the subtype-specific nature of HPC infection, we examined the prevalence of HPC infection in vivo by HIV-1 subtypes A and D. HIV-1 infection of HPC was examined in 40 individuals, 19 infected with subtype A and 21 with subtype D, using a single colony assay format. DNA from 1177 extracted colonies was tested for integrated viral DNA of the p24 gene. Four colonies were found to be stably infected, three of 462 colonies (0.65%) from HIV-1A-infected individuals (1/19 individuals) and one of 715 colonies (0.14%) from HIV-1D-infected individuals (1/22 individuals). These rates of colony infection were comparable to the rates observed in PBMCs from the same subjects. Additionally, no correlation was observed between cell colony density and circulating viral load or proviral load. Our findings suggest that HIV-1 subtypes A and D do not preferentially infect colony-forming HPCs over mature HIV target cells in vivo.
Vaginal Cytomegalovirus Shedding Before and After Initiation of Antiretroviral Therapy in Rakai, Uganda
(The Journal of infectious diseases, 2015) Gianella, Sara; Redd, Andrew D.; Grabowski, Mary K.; Tobian, Aaron A. R.; Serwadda, David; Newell, Kevin; Patel, Eshan U.; Kalibbala, Sarah; Ssebbowa, Paschal; Gray, Ronald H.; Quinn, Thomas C.; Reynolds, Steven J.
Vaginal shedding of cytomegalovirus (CMV) DNA was determined longitudinally among 96 women coinfected with human immunodeficiency virus (HIV), herpes simplex virus 2, and CMV starting antiretroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV RNAviral load before ART initiation, and younger age were significantly associated with increased frequency of CMV shedding (P < .01). Compared to pre- ART, CMV shedding peaked from month 2 to month 4 after ART initiation, suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding.

Browsing by Author "Redd, Andrew D."

Results Per Page

Sort Options